INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ying Wen,Zhen Zou,Yitong Li,Danhua Zhang,Ziru Liu,Hong Liu,Xiejia Li,Wei Wu,Liyun Zeng,Qiongyan Zou,Wenjun Yi
The combination of photodynamic therapy (PDT) and gene therapy is a viable therapeutic approach for the management of secondary hyperparathyroidism (SHPT). Nevertheless, the effective delivery of photosensitizers or nucleotide drugs remains a crucial limitation in achieving therapeutic efficacy. MiR-146b-3p directly targeted BCL2, and its overexpression enhanced the antiproliferative, proautophagic, and proapoptotic effects during 5-aminolevulinic acid (5-ALA)-mediated PDT in this study. Herein, we investigated the potential of codelivering 5-ALA and miR-146b-3p to SHPT primary cells via polyamidoamine (PAMAM) and achieving enhanced therapeutic efficacy relative to that of monotreatment. The fabrication of the PAMAM-based 5-ALA and miR-146b-3p dual-delivery system (5-ALA@PAMAM/miR) involved the use of covalent condensation reactions and electrostatic self-assembly. The nanoparticles were characterized by various analytical techniques, including transmission electron microscopy (TEM), zeta potential measurements, and size measurements. Fluorescence and confocal laser scanning microscopy demonstrated a greater degree of cellular uptake of nanoparticles. Moreover, the synthesized nanoparticles considerably enhanced the effectiveness of PDT without systemic toxicity both in vitro and in vivo. Overall, the nanocarrier-gene-photosensitizer coloaded system is a promising platform for the efficient simultaneous delivery of miR-146b-3p and 5-ALA and achieves synergistic therapeutic effects.
研究领域:
医学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2026
·
IF 7.5
Wen-yuan Zhang,Qian-qian Wei,Tao Zhang,Chunmei Geng,Hai-yan Wu,Chang-shui Wang,Jing Chen,Lei Feng,Pei Jiang
Background and Purpose Despite breakthroughs in immunotherapy and targeted therapies, chemotherapy remains indispensable in oncology. Experimental Approach This study seeks to pinpoint key pathways in doxorubicin (DOX)-treated mouse hippocampus, utilising comprehensive transcriptomic and metabolomic analyses, and validating the mechanisms in vitro and in vivo. Key Results Our multi-omics investigation revealed that sustained DOX exposure induced significant down-regulation of 5-aminolevulinate synthase 2 (ALAS2) and its catalytic product 5-aminolevulinic acid (5-ALA) in the hippocampal region. ALAS2 deficiency was specific to hippocampal neurons, which were more sensitive to oxidative damage than astrocytes or microglia. In vivo and in vitro studies demonstrated that 5-ALA administration or ALAS2 overexpression protected the brain from DOX-induced neurotoxicity. ALAS2 catalyses the condensation of glycine and succinyl-CoA to form 5-ALA, the key precursor of haem. Beyond its role in erythropoiesis, haem is a metabolite that modulates cellular redox homeostasis through interactions with the BACH1 (BTB and CNC homology 1)/NRF2 (nuclear factor erythroid 2 like 2) pathway. We found that DOX suppressed the ALAS2/5-ALA axis, thereby enhancing BACH1 stability. This stabilised BACH1 competes with NRF2 for binding to antioxidant response elements (AREs) in target gene promoters. Conversely, reinforcing the ALAS2/5-ALA axis elevated intracellular haem levels, promoting BACH1 degradation and enhancing NRF2 activity. Using a zebrafish model, we further highlighted the antioxidant and neuroprotective role of 5-ALA against DOX-induced neurotoxicity. Conclusions and Implications In conclusion, this study elucidates a novel endogenous neuroprotective mechanism wherein the ALAS2/5-ALA axis modulates the BACH1/NRF2 pathway. 5-ALA shows promise for repurposing to mitigate chemotherapy-associated neurotoxicity. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLANT CELL TISSUE AND ORGAN CULTURE
·
2018
·Vol. 134
·期 2
·319-330
·
IF 2.004
Zheng Jie,An Yuyan,Wang Liangju
Color is a key factor for fruit commercial value. 5-Aminolevulinic acid (5-ALA), as an eco-friendly plant growth regulator, shows an attractively promotive effect on plant secondary metabolism, especially for fruit coloration. Brassinosteroids (BRs) can also improve plant flavonoid biosynthesis. No information is now available on the relationship between 5-ALA and BR. Here, we found that 1.5 mg L −1 24-epibrassinolide (24-EBL) promoted 50 mg L −1 5-ALA-induced anthocyanin accumulation, while, brassinazole (Brz) significantly inhibited the 5-ALA-induced flavonoid accumulation. HPLC analysis further showed that the inductive effects of 5-ALA on the accumulation of cyanidin-3-galactoside, quercetin-3-galactoside, quercetin and kaempferol were elevated by 24-EBL, but impaired by Brz. These results suggest that brassinolide biosynthesis might involve in 5-ALA-induced flavonoid accumulation. Gene expression analysis showed that 5-ALA and 5-ALA + 24-EBL induced the expression of regulatory genes MdMYB10, MdMYB9, MdbHLH3 and MdbHLH33 . These two treatments also up-regulated the structural gene expressions of anthocyanin biosynthesis and transportation, including MdCHS, MdF3′H, MdDFR, MdANS, MdUFGT, MdGST and MdMATE , as well as flavonol biosynthetic gene MdFLS . But Brz decreased 5-ALA-induced up-regulation of these genes. In addition, 5-ALA also induced the expression of MdBRI1, MdBAK1 and MdBZR1 , which are involved in brassinolide signal transduction. These results indicate that 24-EBL enhances 5-ALA-promoted expression of genes related to flavonoid biosynthesis and brassinolide signal transduction, while Brz exhibits the opposite effects. Taken together, we propose that 24-EBL is involved in 5-ALA-induced anthocyanin and flavonol accumulation in calli of apples. Our results provide new insights into 5-ALA-induced fruit coloration.
研究领域:
植物生理学
·
分子生物学
·
园艺学
✓ 已验证
DOI
高影响因子
Metabolites
·
2024
·Vol. 14
·期 3
·142
·
IF 3.4
Yaxin Wang,Chaolu Tan,Yinghao Li,Fengyan Meng,Youwei Du,Shuyu Zhang,Wenxin Jiang,Naijie Feng,Liming Zhao,Dianfeng Zheng
A large number of dead seedlings can occur in saline soils, which seriously affects the large-scale cultivation of rice. This study investigated the effects of plant growth regulators (PGRs) and nitrogen application on seedling growth and salt tolerance (Oryza sativaL.), which is of great significance for agricultural production practices. A conventional rice variety, “Huang Huazhan”, was selected for this study. Non-salt stress treatments included 0% NaCl (CK treatment), CK + 0.05 g N/pot (N treatment), CK + 40 mg·L−15-aminolevulinic acid (5-ALA) (A treatment), and CK + 30 mg·L−1diethylaminoethyl acetate (DTA-6) (D treatment). Salt stress treatments included 0.3% NaCl (S treatment), N + 0.3% NaCl (NS treatment), A + 0.3% NaCl (AS treatment), and D + 0.3% NaCl (DS treatment). When 3 leaves and 1 heart emerged from the soil, plants were sprayed with DTA-6 and 5-ALA, followed by the application of 0.3% NaCl (w/w) to the soil after 24 h. Seedling morphology and photosynthetic indices, as well as carbohydrate metabolism and key enzyme activities, were determined for each treatment. Our results showed that N, A, and D treatments promoted seedling growth, photosynthesis, carbohydrate levels, and the activities of key enzymes involved in carbon metabolism when compared to the CK treatment. The A treatment had the most significant effect, with increases in aboveground dry weight and net photosynthetic rates (Pn) ranging from 17.74% to 41.02% and 3.61% to 32.60%, respectively. Stomatal limiting values (Ls) significantly decreased from 19.17% to 43.02%. Salt stress significantly inhibited seedling growth. NS, AS, and DS treatments alleviated the morphological and physiological damage of salt stress on seedlings when compared to the S treatment. The AS treatment was the most effective in improving seedling morphology, promoting photosynthesis, increasing carbohydrate levels, and key enzyme activities. After AS treatment, increases in aboveground dry weight, net photosynthetic rate, soluble sugar content, total sucrose synthase, and amylase activities were 17.50% to 50.79%, 11.39% to 98.10%, 20.20% to 80.85%, 21.21% to 33.53%, and 22.17% to 34.19%, respectively, when compared to the S treatment. In summary, foliar sprays of 5-ALA, DTA-6, and additional nitrogen fertilizer enhanced rice seedling growth, increased photosynthesis, lowered Ls values, and improved seedling salt tolerance. Spraying two regulators, 5-ALA and DTA-6, quantitatively increased the effect of nitrogen fertilizer, with comparable effects on NaCl stress regulation. This study provides the basis for efficient agricultural production.
研究领域:
植物生理学
·
农业科学
·
胁迫生物学
·
作物科学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hai-Yun Zhang,Guifang Wang,Yuxin Li,Ying Wen,Yan Zhang,Qiangsong Wang
The combination of multiple anti-tumor methods has shown significant application potential in overcoming the limitations of monotherapy. Photodynamic therapy (PDT) and chemotherapy combination is a promising strategy for reducing drug resistance and side effects. Here, inspired by the acidic environment of tumors, carboxymethyl chitosan-based pH-responsive nanovesicles were developed to co-deliver the chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5-aminolevulinic acid (5-ALA). The in vitro drug release studies revealed that drugs could be responsively released when nanoparticles were triggered by the acidic environment. The controlled-release behavior improved drug retention and reduced the administration time. Our nanoparticles could significantly enhance the killing effect of drugs on tumor cells and increase intracellular levels of reactive oxygen species (ROS) compared to monotherapy, effectively achieving the effects of combined chemotherapy and PDT. The loaded DOX could kill tumor cells and the loaded 5-ALA could enhance the content of protoporphyrin IX (PpIX), resulting in excess ROS production to improve the effects of PDT. In summary, our nanoparticles could co-deliver the drugs and exert synergistical anti-tumor of PDT and chemotherapy by suppressing tumor cell proliferation and facilitating cell apoptosis.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Xiao Liu,Yuan Zhang,Peng Zhang,Kang Ge,Ruzhi Zhang,Yixin Sun,Yang Sheng,Mark Bradley,Rong Zhang
Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an important approach for the treatment of some skin diseases and cancers. A major defect of this approach is that it is difficult for 5-ALA to accumulate around lesions in deeper regions of tissue, resulting in poor conversion to the active fluorophore and photodynamic efficiencies. Because of their targeting and controlled release abilities, nanogel carriers could solve this problem. In this paper, nanogels were prepared by using micro-emulsion polymerization with various biodegradable polyester crosslinkers ( L -lactide and ε-caprolactone). The swelling and degradation properties and entrapment efficiency, drug loading and drug release ability of the nanogels were investigated. Nanogels co-cultured with skin cancer cells (A2058) allowed the efficiency of the PDT in vitro to be demonstrated. The results showed that the swelling rate of hydrogels reduced with increasing crosslinker levels, which caused a slow-down in the release of 5-ALA, but lipase accelerated degradation of nanogels increased 5-ALA concentrations in tumor cells and leading to higher PDT efficiency. It was proved by in vivo experiment indicating that the development of skin cancer tissues were efficiently inhibited by the 5-ALA loaded nanogels.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
·
2023
·Vol. 22
·期 4
·905-917
·
IF 3.1
Wen Ying,Zeng Liyun,Chen Qitong,Li Yitong,Fu Mengdie,Wang Zixin,Liu Hong,Li Xiejia,Huang Peng,Wu Wei,Zou Qiongyan,Yi Wenjun
Background The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. Methods Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. Results In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM–receptor interaction, focal adhesion and protein digestion and absorption. Protein–protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. Conclusions The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT. Graphical abstract
研究领域:
转录组学
·
光动力疗法
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）